Projects and Grants per year
Grants and Contracts Details
Description
The standard of care for AD patients has only incrementally improved in the last decade with AD
patients still suffering from a slow and inevitable decline in cognitive function and
neurodegeneration. Glucose hypo-metabolism occurs in almost all AD cases and defining the
mechanism could provide a novel AD therapeutic target. Our compelling preliminary data
suggest aberrant AD-PGBs modulate glucose metabolism and we have developed VAL-0417 as
a pre-clinical treatment to ablate the AD-PGBs.
Recent human studies suggest that age-related cognitive decline, AD risk, and preclinical
AD amyloid plaque pathology are more strongly associated with increased sleep fragmentation
than with total sleep loss. Fragmentation of the daily sleep-wake rhythm is associated with
greater risk of incident AD and earlier cognitive decline in older humans, and this association
remains even after controlling for the total daily rest time, medical history, and demographic
factors. Preclinical AD pathology is also associated with fragmentation of the daily rest-activity
rhythm in middle-aged and older humans. Additionally, our preliminary data demonstrate that
AD-related mouse models, including 5xFAD, exhibit increased Aβ accumulation and
neuroinflammation with sleep fragmentation.
AD hypo-metabolism is likely connected to AD sleep dysfunction, but the mechanistic nature
of this association is unknown. We postulate that the Gentry and Murphy labs can capitalize on
our individual areas of expertise to understand the integrative physiology of sleep and sleep
disruption on AD using cutting-edge technology, including metabolomics and RNAseq, while
evaluating a putative novel target for AD prevention. Per NOT-NS-21-040, Drs. Gentry and
Murphy have not previously collaborated or published together.
Status | Finished |
---|---|
Effective start/end date | 5/15/20 → 4/30/22 |
Funding
- National Institute of Neurological Disorders & Stroke
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Projects
- 1 Finished
-
Brain Glycogen - Metabolism, Mechanisms, and Therapeutic Potential
Gentry, M. (PI), Johnson, L. (CoI), Nelson, P. (CoI), Sun, R. (CoI), Vander Kooi, C. (CoI) & Zhu, H. (CoI)
National Institute of Neurological Disorders & Stroke
5/15/20 → 4/30/22
Project: Research project